A Genome-wide Trans-ethnic Interaction Study Links the PIGR-FCAMR Locus to Coronary Atherosclerosis Via Interactions Between Genetic Variants and Residential Exposure to Traffic
Citation:
Ward-Caviness, C., L. Neas, C. Blach, C. Haynes, K. LaRocque-Abramson, E. Grass, E. Dowdy, R. Devlin, D. Diaz-Sanchez, W. Cascio, M. Miranda, S. Gregory, S. Shah, W. Kraus, AND E. Hauser. A Genome-wide Trans-ethnic Interaction Study Links the PIGR-FCAMR Locus to Coronary Atherosclerosis Via Interactions Between Genetic Variants and Residential Exposure to Traffic. PLOS ONE . Public Library of Science, San Francisco, CA, 12(3):e0173880, (2017).
Impact/Purpose:
Cardiovascular disease accounts for about a third of all U.S. deaths. Living near major roadways increases the risk of cardiovascular disease. The manuscript describes the results of a genome-wide search for new coronary atherosclerosis genes based on their modification of the association between degree of coronary artery occlusion and residential exposure to traffic. Under the Clean Air Act, ambient air standards are required to be set at a level sufficient to protect the health of “sensitive groups.” Identifying novel genes that increase traffic-induced cardiac effects may help identify these sensitive groups.
Description:
Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic air pollution is a ubiquitous source of air pollution in developed nations, and is associated with multiple cardiovascular outcomes such as: coronary atherosclerosis, peripheral arterial disease, and myocardial infarction. Despite the recognition of the importance of both genetic and environmental exposures to the pathogenesis of cardiovascular disease, studies of these two contributors jointly are rare. We performed a genome-wide interaction study (GWIS) to examine gene-traffic exposure interactions associated with coronary atherosclerosis. Using race-stratified cohorts of 554 African-Americans (AA) and 1623 European-Americans (EA) from a cardiac catheterization cohort (CATHGEN), we identify gene-by-traffic exposure interactions associated with the number of significantly diseased coronary vessels as a measure of chronic atherosclerosis. We found five suggestive (P<1x10-5) interactions in the AA GWIS, of which two (rs1856746 and rs2791713) replicated in the EA cohort (P < 0.05). Both SNPs are in the PIGR-FCAMR locus and are eQTLs in lymphocytes. The protein products of both PIGR and FCAMR are implicated in inflammatory processes. In the EA GWIS, there were three suggestive interactions; none of these replicated in the AA GWIS. All three were intergenic; the most significant interaction was in a regulatory region associated with SAMSN1, a gene previously associated with atherosclerosis and B cell activation. In conclusion, we have uncovered several novel genes associated with coronary atherosclerosis in individuals chronically exposed to increased ambient concentrations of traffic air pollution. These genes point towards inflammatory pathways which may modify the effects of air pollution on cardiovascular disease risk.
